The objectives of this proposal are to determine the serum levels of protein SAA in neoplastic diseases, relate these data to diagnosis and prognosis, and define the relationship of this protein to the immune dysfunctions noted in cancer. This protein (SAA) which is the precursor of secondary amyloid is present in all normal sera and has been shown to be increased in a number of acute and chronic diseases as well as in cancer. SAA in the murine model of secondary amyloidosis has previously been shown to suppress the formation of antibody in in vitro cultures of splenic lymphocytes. SAA levels will be determined by radioimmunossay using radiolabeled amyloid protein AA and antiserum specific for AA. Sera will be collected from patients with cancer of lung, bowel, breast and lymphoma at the time of initial diagnosis and at periodic intervals thereafter. SAA levels will be correlated with type of tumor, response to therapy, and presence or absence of recurrent tumor. A relationship between SAA levels and lymphocyte dysfunction as measured by mitogen stimulation and T and B cell enumeration will be sought. The effect of SAA on the in vitro formation of antibody by human lymphocytes will be evaluated by either culturing peripheral blood lymphocytes in the Mishell-Dutton system using an insolubilized antigen (TNP-PAA) or by culturing human tonsillar lymphocytes in the Marbrook system using TNP-KLH as the antigen. Cancer serum before and after absorption with antiserum to protein AA will be added to cultures to determine the effect of SAA on the cell antibody responses. The objectives of these experiments are: (1) to show whether SAA can cause suppression of immune function in the human as it can in the murine system and, therefore, that it may play an important role in the host-tumor relationship; and (2) to evaluate if SAA has any role in the depressed immunoglobulin synthesis by B cells in multiple myeloma.